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Involvement of B 1 and B 2 receptors in bradykinin‐induced rat paw oedema
Author(s) -
Campos Maria M.,
Calixto João B.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb13305.x
Subject(s) - bradykinin , chemistry , substance p , calcitonin gene related peptide , ed50 , receptor , endocrinology , agonist , medicine , pharmacology , prostaglandin d2 , prostaglandin , prostaglandin e2 receptor , histamine , prostaglandin e2 , neuropeptide
1 The mechanisms involved in bradykinin (BK)‐induced oedema in the rat paw as well as the interactions between BK and several inflammatory mediators, have been investigated. 2 Intraplantar injection of BK (1 nmol/paw) in rats pretreated with captopril (5 mg kg −1 , s.c.) caused a small amount of oedema formation (0.17 ± 0.05 ml). Des‐Arg 9 ‐BK (DABK, a selective B 1 receptor agonist) up to 300 nmol/paw caused minimal oedema (0.03 ± 0.01 ml). 3 Co‐administration of prostaglandin E 2 (PGE 2 ), prostaglandin I 2 (PGI 2 ), calcitonin gene‐related peptide (CGRP), 5‐hydroxytryptamine (5‐HT), substance P (SP) or platelet activating factor (PAF) (1 pmol–1 nmol/paw) with BK (1 nmol/paw) dose‐dependently potentiated BK‐induced paw oedema. The rank order of potency (mean ED 50 , pmol/paw) for this effect was: SP (8.1) > PAF (13.7) > PGI 2 (20.5) > 5‐HT (23.8) > CGRP (25.7) > PGE 2 (52.0). Co‐administration of BK with the various inflammatory mediators resulted in maximal paw oedemas (ml) of: PGE 2 (0.71 ± 0.02); PGI 2 (0.66 ± 0.02); 5‐HT (0.65 ± 0.01); SP (0.63 ± 0.05); CGRP (0.60 ± 0.05) and PAF (0.47 ± 0.02) ml. Histamine (up to 1 nmol/paw) was ineffective in potentiating the response to BK. 4 Hoe 140 or NPC 17731 (two selective B 2 receptor antagonists, 0.1–3 nmol/paw) produced dose‐dependent inhibition of paw oedema potentiation induced by co‐injection of BK with other mediators with the following mean ID 50 s (nmol/paw): Hoe 140–1.4; 1.3; 1.5 and 1.1 and NPC 17731–1.0; 1.0; 0.9 and 0.7; in the presence of PGE 2 , PGI 2 , CGRP and SP, respectively. The selective B 1 receptor antagonist des‐Arg 9 [Leu 8 ]‐BK (DALBK, up to 300 nmol/paw) had no effect. 5 Daily intraplantar injections of BK (10 nmol/paw) once a day for 7 consecutive days caused a progressive and complete desensitization of the paw oedema, which was specific for BK, since paw oedema induced by PAF, PGE 2 , SP or histamine was not affected. In addition, the oedema caused by BK in the paw desensitized to the peptide was almost completely reversed if BK was co‐injected with PGE 2 , PGI 2 or SP (1 nmol/paw). Injection of PGE 2 or SP (10 nmol/paw) together with the first BK injection (10 nmol/paw), partially prevented BK‐induced desensitization. 6 When animals were completely desensitized to BK, DABK (100 nmol/paw) caused paw oedema (0.25 ± 0.03 ml) which was consistently blocked by the B 1 receptor antagonist, DALBK (100 nmol/paw). 7 Treatment of animals with dexamethasone (0.5 mg kg −1 , s.c., 24 h previously) antagonized paw oedema induced by DABK (100 nmol/paw) in desensitized paws, but not that induced by BK (3 nmol/ paw) in naive paws. The steroid also prevented the recovery of oedema seen after co‐injection of BK with PGE 2 or PGI 2 (1 nmol/paw) in desensitized paws. 8 These results suggest that both B 1 and B 2 receptors are involved in BK‐induced rat paw oedema. The B 2 receptors are constitutive, but induction of expression of B 1 receptors seems to occur only after complete desensitization of the paw to BK. In addition, very low doses of inflammatory mediators markedly potentiate BK‐induced paw oedema and can attenuate BK‐induced paw oedema desensitization. Such mechanisms may be relevant for the manifestation of acute and chronic inflammatory processes.